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PloS One 2022To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014.
OBJECTIVE
To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014.
METHODS
We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the Clinical Practice Research Datalink from the United Kingdom, and the IBM MarketScan Research Databases from the United States. We included pregnancies ending in live births, stillbirth, spontaneous abortion, or induced abortion. We determined maternal use of antiemetics from pharmacy claims in Canada and the United States and from prescriptions in the United Kingdom.
RESULTS
The most common outcome of 3 848 734 included pregnancies (started 2002-2014) was live birth (66.7% of all pregnancies) followed by spontaneous abortion (20.2%). Use of antiemetics during pregnancy increased over time in all three countries. Canada had the highest prevalence of use of prescription antiemetics during pregnancy (17.7% of pregnancies overall, 13.2% of pregnancies in 2002, and 18.9% in 2014), followed by the United States (14.0% overall, 8.9% in 2007, and 18.1% in 2014), and the United Kingdom (5.0% overall, 4.2% in 2002, and 6.5% in 2014). Besides use of antiemetic drugs being considerably lower in the United Kingdom, the increase in its use over time was more modest. The most commonly used antiemetic was combination doxylamine/pyridoxine in Canada (95.2% of pregnancies treated with antiemetics), ondansetron in the United States (72.2%), and prochlorperazine in the United Kingdom (63.5%).
CONCLUSIONS
In this large cohort study, we observed an overall increase in antiemetic use during pregnancy, and patterns of use varied across jurisdictions. Continued monitoring of antiemetic use and further research are warranted to better understand the reasons for differences in use of these medications and to assess their benefit-risk profile in this population.
Topics: Pregnancy; Female; Humans; Antiemetics; Abortion, Spontaneous; Cohort Studies; Retrospective Studies; Gastrointestinal Agents; Alberta
PubMed: 36454900
DOI: 10.1371/journal.pone.0277623 -
Frontiers in Oncology 2023The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One... (Review)
Review
The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One promising avenue lies in the repurposing of existing drugs. This review explores the impact of phenothiazines, primarily used as antipsychotic agents, on key mechanisms driving tumor growth and metastasis. The cationic and amphiphilic nature of phenothiazines allows interaction with the lipid bilayer of cellular membranes, resulting in alterations in lipid composition, modulation of calcium channels, fluidity, thinning, and integrity of the plasma membrane. This is especially significant in the setting of increased metabolic activity, a higher proliferative rate, and the invasiveness of cancer cells, which often rely on plasma membrane repair. Therefore, properties of phenothiazines such as compromising plasma membrane integrity and repair, disturbing calcium regulation, inducing cytosolic K-RAS accumulation, and sphingomyelin accumulation in the plasma membrane might counteract multidrug resistance by sensitizing cancer cells to membrane damage and chemotherapy. This review outlines a comprehensive overview of the mechanisms driving the anticancer activities of phenothiazines derivates such as trifluoperazine, prochlorperazine, chlorpromazine, promethazine, thioridazine, and fluphenazine. The repurposing potential of phenothiazines paves the way for novel approaches to improve future cancer treatment.
PubMed: 38074670
DOI: 10.3389/fonc.2023.1320621 -
American Family Physician May 2014
Review
Topics: Acute Disease; Adult; Anti-Inflammatory Agents, Non-Steroidal; Antipsychotic Agents; Dexamethasone; Dopamine Antagonists; Droperidol; Emergency Service, Hospital; Glucocorticoids; Humans; Metoclopramide; Migraine Disorders; Practice Guidelines as Topic; Prochlorperazine
PubMed: 24784338
DOI: No ID Found -
The Journal of Pain Oct 2004Recently it has been proposed that the throbbing pain of migraine is mediated by sensitization of peripheral trigeminovascular neurons, and that cutaneous allodynia of... (Comparative Study)
Comparative Study
UNLABELLED
Recently it has been proposed that the throbbing pain of migraine is mediated by sensitization of peripheral trigeminovascular neurons, and that cutaneous allodynia of migraine is mediated by sensitization of central trigeminovascular neurons, and, moreover, that the triptans are less effective in aborting a migraine attack if the central sensitization is already established. The combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) is a drug of well-established use in the acute treatment of migraine. The aim of this study was to investigate whether the 3 active principles of IndoProCaf, alone and combined, compared to sumatriptan, were able to abolish the peripheral sensitization induced by kainic acid and the central sensitization induced by N-methyl-D-aspartate (NMDA) in in vivo models of hyperalgesia. The study showed that indomethacin or IndoProCaf is able to abolish both the kainic acid-induced and the NMDA-induced hyperalgesia. If administered at different times, IndoProCaf was always effective in reversing the kainic acid-induced hyperalgesia. Sumatriptan was not able to reverse either the kainic acid-induced or the NMDA-induced hyperalgesia. The efficacy of indomethacin, alone and combined with prochlorperazine and caffeine, in abolishing peripheral and central sensitization in in vivo models of hyperalgesia is a further explanation of the clinical efficacy of IndoProCaf in the treatment of migraine.
PERSPECTIVE
This study suggests that, although triptans were shown to be able to abort migraine attacks only if given before the establishment of cutaneous allodynia and central sensitization, IndoProCaf should be able to abort migraine attacks independently from the time of administration, because it is able to abolish an already established peripheral and central sensitization.
Topics: Animals; Caffeine; Disease Models, Animal; Drug Therapy, Combination; Indomethacin; Male; Mice; Migraine Disorders; Pain Measurement; Peripheral Nerves; Prochlorperazine; Sumatriptan; Trigeminal Nerve
PubMed: 15501422
DOI: 10.1016/j.jpain.2004.06.008 -
Acta Neurologica Taiwanica Jun 2017In 2015, the American Headache Society (AHS) amended the treatment guideline of acute migraine based on evidence-based medicine (EBM) that all triptans in any form of...
In 2015, the American Headache Society (AHS) amended the treatment guideline of acute migraine based on evidence-based medicine (EBM) that all triptans in any form of preparations, acetaminophen, and non-steroid anti-inflammation drugs-NSAID (aspirin, diclofenac, ibuprofen, naproxen), sumatriptan/naproxen, combined acetaminophen/aspirin/caffeine are considered effective (Level A). Previously effective drugs as prochlorperazine, and dihydroergotamine-DHE (excluded inhaled form) were downrated to probable effective (Level B). Taiwan Headache Society published its treatment guideline for acute migraine attack in 2007. It should be updated based on the new available evidence. The Treatment Guideline Subcommittee of Taiwan Headache Society reviewed the recent trials, evaluated the grade of evidence, and appraised the clinical efficacy to reach a new consensus. We also referred to the guidelines from United States, Europe, Canada and other countries to make this one meets our needs and feasible. Acute medications currently available in Taiwan can be categorized into "migraine-specific"and"migraine-nonspecific" groups. Migraine-specific triptans and migraine-nonspecific nonsteroidal antiinflammatory drugs (NSAIDs) have the best levels of evidence, and are recommended as the first-line medications for acute migraine attacks. The administration should follow the concept of "stratified care". For mild to moderate migraine attacks, oral NSAIDs are the first choice; with oral aspirin, combination analgesics, intravenous/intramuscular NSAIDs as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine/caffeine compounds are recommended and should be administered in the early stage of migraine attacks. Antiemetics can be used as supplement to alleviate nausea and vomiting. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either therapy alone. Parenteral steroid and fluid supply are the first choice in treatment of status migrainosus. Acetaminophen is suitable for mild to moderate migraine attacks and remains the first choice for children and pregnant women. Opiates are not recommended for acute migraine treatment at the present time because of serious adverse events. To prevent medication-overuse headache, the use of acute treatment should be limited to a maximum of ten days a month.
Topics: Acute Disease; Anti-Inflammatory Agents, Non-Steroidal; Humans; Migraine Disorders; Practice Guidelines as Topic; Tryptamines
PubMed: 29250761
DOI: No ID Found -
Frontiers in Cell and Developmental... 2017The growing resistance of leishmaniasis to first-line drugs like antimonials in some regions limits the control of this parasitic disease. The precise mechanisms...
The growing resistance of leishmaniasis to first-line drugs like antimonials in some regions limits the control of this parasitic disease. The precise mechanisms involved in antimony resistance are still subject to debate. The reduction of intracellular Sb accumulation is a common change observed in both laboratory-selected and field isolated resistant strains, but the exact transport pathways involved in antimony resistance have not yet been elucidated. In order to functionally characterize the antimony transport routes responsible for resistance, we performed systematic transport studies of Sb in wild-type and resistant strains of . () and . (. Those include influx and efflux assays and the influence of ABC transporters and metabolism inhibitors: prochlorperazine, probenecid, verapamil, BSO, and sodium azide. The mRNA levels of genes associated with antimony resistance (, and ) were also investigated in addition to intracellular thiol levels. A strong reduction of Sb influx was observed in resistant mutant (LgSbR), but not in (LbSbR). Both mutants showed increased energy-dependent efflux of Sb, when compared to their respective parental strains. In LgSbR, BSO and prochlorperazine inhibited antimony efflux and resistance was associated with increased and mRNA levels, while in LbSbR antimony efflux was inhibited by probenicid and prochlorperazine in absence of resistance-associated gene modulation. Intracellular thiol levels were increased in both Sb-resistant mutants. An energy-dependent Sb efflux pathway sensitive to prochlorperazine was clearly evidenced in both Sb-resistant mutants. In conclusion, the present study allowed the biophysical and pharmacological characterization of energy-dependent Sb efflux pathway apparently independent of MRPA, ABCI4, and ARM58 upregulation, in (Vianna) mutant selected for resistance to Sb. Prochlorperazine has also been identified as an effective chemosensitizer in both Sb resistant mutants, which acts through inhibition of the active efflux of Sb.
PubMed: 28393067
DOI: 10.3389/fcell.2017.00024 -
The Cochrane Database of Systematic... Sep 2015Nausea and vomiting is a common and distressing presenting complaint in emergency departments (ED). The aetiology of nausea and vomiting in EDs is diverse and drugs are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nausea and vomiting is a common and distressing presenting complaint in emergency departments (ED). The aetiology of nausea and vomiting in EDs is diverse and drugs are commonly prescribed. There is currently no consensus as to the optimum drug treatment of nausea and vomiting in the adult ED setting.
OBJECTIVES
To provide evidence of the efficacy and safety of antiemetic medications in the management of nausea and vomiting in the adult ED setting.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8), MEDLINE (OvidSP) (January 1966 to August 2014), EMBASE (OvidSP) (January 1980 to August 2014) and ISI Web of Science (January 1955 to August 2014). We also searched relevant clinical trial registries and conference proceedings.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of any drug in the treatment of nausea and vomiting in the treatment of adults in the ED. Study eligibility was not restricted by language or publication status.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We contacted authors of studies to obtain missing information if required.
MAIN RESULTS
We included eight trials, involving 952 participants, of which 64% were women. Included trials were generally of adequate quality, with six trials at low risk of bias, and two trials at high risk of bias. Three trials with 518 participants compared five different drugs with placebo; all reported the primary outcome as mean change in visual analogue scale (VAS) (0 to 100) for nausea severity from baseline to 30 minutes. Trials did not routinely report other primary outcomes of the change in nausea VAS at 60 minutes or number of vomiting episodes. Differences in mean VAS change from baseline to 30 minutes between placebo and the drugs evaluated were: metoclopramide (three trials, 301 participants; mean difference (MD) -5.27, 95% confidence interval (CI) -11.33 to 0.80), ondansetron (two trials, 250 participants; MD -4.32, 95% CI -11.20 to 2.56), prochlorperazine (one trial, 50 participants; MD -1.80, 95% CI -14.40 to 10.80), promethazine (one trial, 82 participants; MD -8.47, 95% CI -19.79 to 2.85) and droperidol (one trial, 48 participants; MD -15.8, 95% CI -26.98 to -4.62). The only statistically significant change in baseline VAS to 30 minutes was for droperidol, in a single trial of 48 participants. No other drug was statistically significantly superior to placebo. Other included trials evaluated a drug compared to "active controls" (alternative antiemetic). There was no convincing evidence of superiority of any particular drug compared to active control. All trials included in this review reported adverse events, but they were variably reported precluding meaningful pooling of results. Adverse events were generally mild, there were no reported serious adverse events. Overall, the quality of the evidence was low, mainly because there were not enough data.
AUTHORS' CONCLUSIONS
In an ED population, there is no definite evidence to support the superiority of any one drug over any other drug, or the superiority of any drug over placebo. Participants receiving placebo often reported clinically significant improvement in nausea, implying general supportive treatment such as intravenous fluids may be sufficient for the majority of people. If a drug is considered necessary, choice of drug may be dictated by other considerations such as a person's preference, adverse-effect profile and cost. The review was limited by the paucity of clinical trials in this setting. Future research should include the use of placebo and consider focusing on specific diagnostic groups and controlling for factors such as intravenous fluid administered.
Topics: Adult; Antiemetics; Droperidol; Emergency Service, Hospital; Female; Humans; Male; Metoclopramide; Nausea; Ondansetron; Prochlorperazine; Promethazine; Randomized Controlled Trials as Topic; Visual Analog Scale; Vomiting
PubMed: 26411330
DOI: 10.1002/14651858.CD010106.pub2 -
Journal of Managed Care Pharmacy : JMCP May 2005To compare the cost-effectiveness of 2 antiemetic agents, ondansetron and prochlorperazine, for the prevention of postoperative nausea and vomiting (PONV) in patients...
OBJECTIVE
To compare the cost-effectiveness of 2 antiemetic agents, ondansetron and prochlorperazine, for the prevention of postoperative nausea and vomiting (PONV) in patients undergoing total hip replacement or total knee replacement procedures.
METHODS
The cost-effectiveness analysis model was applied to data derived from a previous clinical study conducted in 1995 and 1996. This study involved 78 adult patients (62.8% female and 37.2% male) undergoing total hip replacement or total knee replacement procedures. Patients were enrolled in a randomized, double-blind manner to receive either ondansetron 4 mg intrvenously (n=37) or prochlorperazine 10 mg intramuscularly (n=41) immediately upon completion of surgery and were monitored for occurrences of PONV during the subsequent 48 hours. In our analysis, we measured the cost-effectiveness ratio (C/E ratio), defined as the cost per successfully treated patient, for each antiemetic agent using the clinical data obtained from the previous study.
RESULTS
The incidence of PONV and use of rescue antiemetics was significantly greater in the ondansetron group compared with the prochlorperazine group. The mean total costs of PONV management per patient in the prochlorperazine and ondansetron groups were dollar 13.99 and dollar 51.98, respectively (based on 2004 average wholesale prices [AWP]). The cost of successfully treating one patient with prochlorperazine and ondansetron was dollar 31.87 and dollar 275.01, respectively. One-way sensitivity analysis was performed adjusting the percent efficacy rate of each antiemetic and the drug cost of ondansetron (up to a 50% reduction in AWP). Prochlorperazine remained the dominant strategy across each scenario.
CONCLUSION
The results indicate that prochlorperazine is a more cost-effective antiemetic compared with ondansetron for the prevention of PONV in a mixed gender, adult inpatient population undergoing total joint arthroplasty.
Topics: Antiemetics; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Female; Humans; Male; Middle Aged; Ondansetron; Postoperative Nausea and Vomiting; Prochlorperazine; Randomized Controlled Trials as Topic
PubMed: 15871642
DOI: 10.18553/jmcp.2005.11.4.317 -
Cell Mar 2020Monoclonal antibodies (mAbs) targeting antigens expressed at the surface of tumor cells are widely used for cancer control in clinics, but these treatments need to be...
Monoclonal antibodies (mAbs) targeting antigens expressed at the surface of tumor cells are widely used for cancer control in clinics, but these treatments need to be improved. Chew et al. show how an old drug, prochlorperazine, could be repurposed to enhance the efficacy of anti-tumor mAbs by increasing the cell-surface expression of tumor antigens.
Topics: Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Antigens, Neoplasm; Endocytosis; Humans; Neoplasms
PubMed: 32142673
DOI: 10.1016/j.cell.2020.02.025